Is FTCD p.Thr407Lys (c.1220C>A) pathogenic?

FTCD p.Thr407Lys (c.1220C>A) is classified Benign/Likely benign in FTCD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1022); Rare (popmax 0.535%, mid); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Thr407Lys (c.1220C>A)?

FTCD p.Thr407Lys (c.1220C>A) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Thr407Lys (c.1220C>A) in the general population?

FTCD p.Thr407Lys (c.1220C>A) is rare (popmax 0.535%, mid) (gnomAD).

How is Formiminoglutamic aciduria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FTCD p.Thr407Lys (c.1220C>A)?

AlphaMissense predicts likely benign (score 0.1022) — an in-silico prediction, not a clinical call.

FTCD p.Thr407Lys

c.1220C>A · rs148920158 · VCV340422

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1022 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.535%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.1022	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -8.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP 0.35
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	5.086	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.535% Middle Eastern · 32/5,976 alleles

Filtering AF 0.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.34%

Overall 0.133% 2,077/1,560,728 alleles · rare exomes 1,910/1,408,450 · genomes 167/152,278 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.26%	44
Middle Easterngrpmax	0.535%	187
Remaining individualsnot grpmax-eligible	0.258%	388
European (non-Finnish)	0.101%	987
Admixed American	0.0843%	1,186
South Asian	0.0177%	5,650
African / African-American	0.0136%	7,356
Finnishnot grpmax-eligible	0.00516%	19,384

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FTCD
Protein: p.Thr407Lys
Coding: c.1220C>A
MANE Select: NM_206965
dbSNP: rs148920158
Type: single nucleotide variant
Location: chr21:46145457 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 407: the 'cyclodeaminase/cyclohydrolase' region

Full FTCD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

formiminoglutamic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Formiminoglutamic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

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FTCD p.Ala108Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala159Val Uncertain significance ★★ ⚠ same condition
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FTCD p.Ala418Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala455Thr Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ftcd-p-thr407lys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown